UNASSIGNED: Anterior cruciate ligament injury of the knee is common and leads to decreased activity and risk of secondary osteoarthritis of the knee. Management of patients with a non-acute anterior cruciate ligament injury can be non-surgical (rehabilitation) or surgical (reconstruction). However, insufficient evidence exists to guide treatment.
UNASSIGNED: To determine in patients with non-acute anterior cruciate ligament injury and symptoms of instability whether a strategy of surgical management (reconstruction) without prior rehabilitation was more clinically and cost-effective than non-surgical management (rehabilitation).
UNASSIGNED: A pragmatic, multicentre, superiority, randomised controlled trial with two-arm parallel groups and 1:1 allocation. Due to the nature of the interventions, no blinding could be carried out.
UNASSIGNED: Twenty-nine NHS orthopaedic units in the United Kingdom.
UNASSIGNED: Participants with a symptomatic (instability) non-acute anterior cruciate ligament-injured knee.
UNASSIGNED: Patients in the surgical management arm underwent surgical anterior cruciate ligament reconstruction as soon as possible and without any further rehabilitation. Patients in the rehabilitation arm attended physiotherapy sessions and only were listed for reconstructive surgery on continued instability following rehabilitation. Surgery following initial rehabilitation was an expected outcome for many patients and within protocol.
UNASSIGNED: The primary outcome was the Knee Injury and Osteoarthritis Outcome Score 4 at 18 months post randomisation. Secondary outcomes included return to sport/activity, intervention-related complications, patient satisfaction, expectations of activity, generic health quality of life, knee-specific quality of life and resource usage.
UNASSIGNED: Three hundred and sixteen participants were recruited between February 2017 and April 2020 with 156 randomised to surgical management and 160 to rehabilitation. Forty-one per cent (n = 65) of those allocated to rehabilitation underwent subsequent reconstruction within 18 months with 38% (n = 61) completing rehabilitation and not undergoing surgery. Seventy-two per cent (n = 113) of those allocated to surgery underwent reconstruction within 18 months. Follow-up at the primary outcome time point was 78% (n = 248; surgical, n = 128; rehabilitation, n = 120). Both groups improved over time. Adjusted mean Knee Injury and Osteoarthritis Outcome Score 4 scores at 18 months had increased to 73.0 in the surgical arm and to 64.6 in the rehabilitation arm. The adjusted mean difference was 7.9 (95% confidence interval 2.5 to 13.2; p = 0.005) in favour of surgical management. The per-protocol analyses supported the intention-to-treat results, with all treatment effects favouring surgical management at a level reaching statistical significance. There was a significant difference in Tegner Activity Score at 18 months. Sixty-eight per cent (n = 65) of surgery patients did not reach their expected activity level compared to 73% (n = 63) in the rehabilitation arm. There were no differences between groups in surgical complications (n = 1 surgery, n = 2 rehab) or clinical events (n = 11 surgery, n = 12 rehab). Of surgery patients, 82.9% were satisfied compared to 68.1% of rehabilitation patients. Health economic analysis found that surgical management led to improved health-related quality of life compared to non-surgical management (0.052 quality-adjusted life-years, p = 0.177), but with higher NHS healthcare costs (£1107, p < 0.001). The incremental cost-effectiveness ratio for the surgical management programme versus rehabilitation was £19,346 per quality-adjusted life-year gained. Using £20,000-30,000 per quality-adjusted life-year thresholds, surgical management is cost-effective in the UK setting with a probability of being the most cost-effective option at 51% and 72%, respectively.
UNASSIGNED: Not all surgical patients underwent reconstruction, but this did not affect trial interpretation. The adherence to physiotherapy was patchy, but the trial was designed as pragmatic.
UNASSIGNED: Surgical management (reconstruction) for non-acute anterior cruciate ligament-injured patients was superior to non-surgical management (rehabilitation). Although physiotherapy can still provide benefit, later-presenting non-acute anterior cruciate ligament-injured patients benefit more from surgical reconstruction without delaying for a prior period of rehabilitation.
UNASSIGNED: Confirmatory studies and those to explore the influence of fidelity and compliance will be useful.
UNASSIGNED: This trial is registered as Current Controlled Trials ISRCTN10110685; ClinicalTrials.gov Identifier: NCT02980367.
UNASSIGNED: This award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/140/63) and is published in full in Health Technology Assessment; Vol. 28, No. 27. See the NIHR Funding and Awards website for further award information.
The study aimed to find out whether it is better to offer surgical reconstruction or rehabilitation first to patients with a more long-standing injury of their anterior cruciate ligament in their knee. This injury causes physical giving way of the knee and/or sensations of it being wobbly (instability). The instability can affect daily activities, work, sport and can lead to arthritis. There are two main treatment options for this problem: non-surgical rehabilitation (prescribed exercises and advice from physiotherapists) or an operation by a surgeon to replace the damaged ligament (anterior cruciate ligament reconstruction). Although studies have highlighted the best option for a recently injured knee, the best management was not known for patients with a long-standing injury, perhaps occurring several months previously. Because the surgery is expensive to the NHS (around £100 million per year), it was also important to look at the costs involved. We carried out a study recruiting 316 non-acute anterior cruciate ligament-injured patients from 29 different hospitals and allocated each patient to either surgery or rehabilitation as their treatment option. We measured how well they did with special function and activity scores, patient satisfaction and costs of treatment. Patients in both groups improved substantially. It was expected that some patients in the rehabilitation group would want surgery if non-surgical management was unsuccessful. Forty-one per cent of patients who initially underwent rehabilitation subsequently elected to have reconstructive surgery. Overall, the patients allocated to the surgical reconstruction group had better results in terms of knee function and stability, activity level and satisfaction with treatment than patients allocated to the non-operative rehabilitation group. There were few problems or complications with either treatment option. Although the surgery was a more expensive treatment option, it was found to be cost-effective in the UK setting. The evidence can be discussed in shared decision-making with anterior cruciate ligament-injured patients. Both strategies of management led to improvement. Although a rehabilitation strategy can be beneficial, especially for recently injured patients, it is advised that later-presenting non-acute and more long-standing anterior cruciate ligament-injured patients undergo surgical reconstruction without necessarily delaying for a period of rehabilitation.

UNASSIGNED: To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of cefiderocol in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform the National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England.
UNASSIGNED: The health benefit of cefiderocol was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients\' mortality risks and health-related quality of life. The clinical effectiveness of cefiderocol relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. Patient-level costs and health outcomes of cefiderocol under various usage scenarios compared with alternative management strategies were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population values using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for cefiderocol.
UNASSIGNED: Among Enterobacterales isolates with the metallo-beta-lactamase resistance mechanism, the base-case network meta-analysis found that cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.32, 95% credible intervals 0.04 to 2.47), but the result was not statistically significant. The other treatments were also associated with lower susceptibility than colistin, but the results were not statistically significant. In the metallo-beta-lactamase Pseudomonas aeruginosa base-case network meta-analysis, cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.44, 95% credible intervals 0.03 to 3.94), but the result was not statistically significant. The other treatments were associated with no susceptibility. In the base case, patient-level benefit of cefiderocol was between 0.02 and 0.15 quality-adjusted life-years, depending on the site of infection, the pathogen and the usage scenario. There was a high degree of uncertainty surrounding the benefits of cefiderocol across all subgroups. There was substantial uncertainty in the number of infections that are suitable for treatment with cefiderocol, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time and rates of emergence of resistance. The population-level benefits varied substantially across the base-case scenarios, from 896 to 3559 quality-adjusted life-years over 20 years.
UNASSIGNED: This work has provided quantitative estimates of the value of cefiderocol within its areas of expected usage within the NHS.
UNASSIGNED: Given existing evidence, the estimates of the value of cefiderocol are highly uncertain.
UNASSIGNED: Future evaluations of antimicrobials would benefit from improvements to NHS data linkages; research to support appropriate synthesis of susceptibility studies; and application of routine data and decision modelling to assess enablement value.
UNASSIGNED: No registration of this study was undertaken.
UNASSIGNED: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Policy Research Programme (NIHR award ref: NIHR135591), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in Health Technology Assessment; Vol. 28, No. 28. See the NIHR Funding and Awards website for further award information.
This project tested new methods for estimating the value to the NHS of an antimicrobial, cefiderocol, so its manufacturer could be paid fairly even if very little drug is used in order to reduce the risk of bacteria becoming resistant to the product. Clinicians said that the greatest benefit of cefiderocol is when used for complicated urinary tract infections and pneumonia acquired within hospitals caused by two types of bacteria (called Enterobacterales and Pseudomonas aeruginosa), with a resistance mechanism called metallo-beta-lactamase. Because there were no relevant clinical trial data, we estimated how effective cefiderocol and alternative treatments were by doing a systematic literature review of studies that grew bacteria from infections in the laboratory and tested the drugs on them. We linked this to data estimating the long-term health and survival of patients. Some evidence was obtained by asking clinicians detailed questions about what they thought the effects would be based on their experience and the available evidence. We included the side effects of the alternative treatments, some of which can cause kidney damage. We estimated how many infections there would be in the UK, whether they would increase over time and how resistance to treatments may change over time. Clinicians told us that they would also use cefiderocol to treat intra-abdominal and bloodstream infections, and some infections caused by another bacteria called Stenotrophomonas. We estimated how many of these infections there would be, and assumed the same health benefits as for other types of infections. The total value to the NHS was calculated using these estimates. We also considered whether we had missed any additional elements of value. We estimated that the value to the NHS was £18–71 million over 20 years. This reflects the maximum the NHS could pay for use of cefiderocol if the health lost as a result of making these payments rather than funding other NHS services is not to exceed the health benefits of using this antimicrobial. However, these estimates are uncertain due to limitations with the evidence used to produce them and assumptions that had to be made.

UNASSIGNED: Health economic assessments are used to determine whether the resources needed to generate net benefit from an antenatal or newborn screening programme, driven by multiple benefits and harms, are justifiable. It is not known what benefits and harms have been adopted by economic evaluations assessing these programmes and whether they omit benefits and harms considered important to relevant stakeholders.
UNASSIGNED: (1) To identify the benefits and harms adopted by health economic assessments in this area, and to assess how they have been measured and valued; (2) to identify attributes or relevance to stakeholders that ought to be considered in future economic assessments; and (3) to make recommendations about the benefits and harms that should be considered by these studies.
UNASSIGNED: Mixed methods combining systematic review and qualitative work.
UNASSIGNED: We searched the published and grey literature from January 2000 to January 2021 using all major electronic databases. Economic evaluations of an antenatal or newborn screening programme in one or more Organisation for Economic Co-operation and Development countries were considered eligible. Reporting quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards checklist. We identified benefits and harms using an integrative descriptive analysis and constructed a thematic framework.
UNASSIGNED: We conducted a meta-ethnography of the existing literature on newborn screening experiences, a secondary analysis of existing individual interviews related to antenatal or newborn screening or living with screened-for conditions, and a thematic analysis of primary data collected with stakeholders about their experiences with screening.
UNASSIGNED: The literature searches identified 52,244 articles and reports, and 336 unique studies were included. Thematic framework resulted in seven themes: (1) diagnosis of screened for condition, (2) life-years and health status adjustments, (3) treatment, (4) long-term costs, (5) overdiagnosis, (6) pregnancy loss and (7) spillover effects on family members. Diagnosis of screened-for condition (115, 47.5%), life-years and health status adjustments (90, 37.2%) and treatment (88, 36.4%) accounted for most of the benefits and harms evaluating antenatal screening. The same themes accounted for most of the benefits and harms included in studies assessing newborn screening. Long-term costs, overdiagnosis and spillover effects tended to be ignored. The wide-reaching family implications of screening were considered important to stakeholders. We observed good overlap between the thematic framework and the qualitative evidence.
UNASSIGNED: Dual data extraction within the systematic literature review was not feasible due to the large number of studies included. It was difficult to recruit healthcare professionals in the stakeholder\'s interviews.
UNASSIGNED: There is no consistency in the selection of benefits and harms used in health economic assessments in this area, suggesting that additional methods guidance is needed. Our proposed thematic framework can be used to guide the development of future health economic assessments evaluating antenatal and newborn screening programmes.
UNASSIGNED: This study is registered as PROSPERO CRD42020165236.
UNASSIGNED: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127489) and is published in full in Health Technology Assessment; Vol. 28, No. 25. See the NIHR Funding and Awards website for further award information.
Every year the NHS offers pregnant women screening tests to assess the chances of them or their unborn baby having or developing a health condition. It also offers screening tests for newborn babies to look for a range of health conditions. The implementation of screening programmes and the care for women and babies require many resources and funding for the NHS, so it is important that screening programmes represent good value for money. This means that the amount of money the NHS spends on a programme is justified by the amount of benefit that the programme gives. We wanted to see whether researchers consider all the important benefits and harms associated with screening of pregnant women and newborn babies when calculating value for money. To do this, we searched all studies available in developed countries to identify what benefits and harms they considered. We also considered the views of parents and healthcare professionals on the benefits and harms screening that creates for families and wider society. We found that the identification of benefits and harms of screening is complex because screening results affect a range of people (mother–baby, parents, extended family and wider society). Researchers calculating the value for money of screening programmes have, to date, concentrated on a narrow range of benefits and harms and ignored many factors that are important to people affected by screening results. From our discussions with parents and healthcare professionals, we found that wider impacts on families are an important consideration. Only one study we looked at considered wider impacts on families. Our work also found that parent’s ability to recognise, absorb and apply new information to understand their child’s screening results or condition is important. Healthcare professionals involve in screening should consider this when supporting families of children with a condition. We have created a list for researchers to identify the benefits and harms that are important to include in future studies. We have also identified different ways researchers can value these benefits and harms, so they are incorporated into their studies in a meaningful way.

UNASSIGNED: The global distribution and trends in the attributable burden of cataract risk have rarely been systematically explored. To guide the development of targeted and accurate cataract screening and treatment strategies, we analyzed the burden of cataract disease attributable to known risk factors.
UNASSIGNED: This study utilized detailed cataract data from the Global Burden of Disease e 2019, and we analyzed disability-adjusted life years (DALYs) e each risk factor from 1990 to 2019. Additionally, we calculated estimated annual percentage changes (EAPCs) during the study period.
UNASSIGNED: The results revealed that from 1990-2019, the global age-standardized DALYs of e attributable to particulate matter pollution, smoking, high fasting glucose plasma and high BMI showed steady downward trends (1990-2009: EAPC = -0.21 [-0.57 -0.14]); 2000-2009: EAPC = -0.95 [-1.01 -0.89]; 2010-2019: EAPC = -1.41 [-1.8 -1.02]). The age-standardized DALYs and mortality caused by each risk factor were highest in the low-middle sociodemographic index (SDI) region (EAPC = -1.77[(-2.19--1.34)]). The overall disease burden of cataracts is lower in males than in females. When analyzing the EAPCs of cataract disease burden for each risk factor individually, we found that the age-standardized disability-adjusted life years caused by particulate matter pollution and smoking decreased (PMP1990-2009: EAPC = -0.53 [-0.9--0.16]; 2000-2009: EAPC = -1.39 [-1.45--1.32]; 2010-2019: EAPC = -2.27 [-2.75--1.79]; smoking 2000 to 2009: EAPC = -1.51 [-1.6--1.43], 2009 to 2019: EAPC = -1.34 [-1.68--1])), while high fasting plasma glucose and high body mass index increased annually (HFPG1990 to 1999: EAPC = 1.27 [0.89-1.65], 2000 to 2009: EAPC = 1.02 [0.82-1.22], 2010-2019: EAPC = 0.44 [0.19-0.68]; HBMI 1990 to 1999: EAPC = 1.65 [1.37-1.94], 2000 to 2009: EAPC = 1.56 [1.43-1.68], 2010-2019: EAPC = 1.47 [1.18-1.77]).
UNASSIGNED: The burden of cataracts caused by ambient particulate matter and smoking is increasing in low, low-middle SDI areas, and specific and effective measures are urgently needed. The results of this study suggest that reducing particulate matter pollution, quitting smoking, controlling blood glucose, and lowering BMI could play important roles in reducing the occurrence of cataracts, especially in older people.

For some communicable endemic diseases (e.g., influenza, COVID-19), vaccination is an effective means of preventing the spread of infection and reducing mortality, but must be augmented over time with vaccine booster doses. We consider the problem of optimally allocating a limited supply of vaccines over time between different subgroups of a population and between initial versus booster vaccine doses, allowing for multiple booster doses. We first consider an SIS model with interacting population groups and four different objectives: those of minimizing cumulative infections, deaths, life years lost, or quality-adjusted life years lost due to death. We solve the problem sequentially: for each time period, we approximate the system dynamics using Taylor series expansions, and reduce the problem to a piecewise linear convex optimization problem for which we derive intuitive closed-form solutions. We then extend the analysis to the case of an SEIS model. In both cases vaccines are allocated to groups based on their priority order until the vaccine supply is exhausted. Numerical simulations show that our analytical solutions achieve results that are close to optimal with objective function values significantly better than would be obtained using simple allocation rules such as allocation proportional to population group size. In addition to being accurate and interpretable, the solutions are easy to implement in practice. Interpretable models are particularly important in public health decision making.

BACKGROUND: This study evaluates the cost-effectiveness of Apixaban and Rivaroxaban, compared to Warfarin, for stroke prevention in patients with non-valvular atrial fibrillation in Iran.
METHODS: A Markov model with a 30-year time horizon was employed to simulate and assess different treatment strategies\' cost-effectiveness. The study population comprised Iranian adults with NVAF, identified through specialist consultations, hospital visits, and archival record reviews. Direct medical costs, direct nonmedical, and indirect costs were included. Quality-adjusted life years (QALY) were assessed using an EQ-5D questionnaire. This study utilized a cost-effectiveness threshold of $11 134 per QALY.
RESULTS: Apixaban demonstrated superior cost-effectiveness compared to Rivaroxaban and Warfarin. Over 30 years, total costs were lower in the Apixaban and Rivaroxaban groups compared to the Warfarin group ($126.18 and $109.99 vs. $150.49). However, Apixaban showed higher total QALYs gained compared to others (0.134 vs. 0.133 and 0.116). The incremental cost-effectiveness ratio for comparing Apixaban to Warfarin was calculated at -1332.83 cost per QALY, below the threshold of $11 134, indicating Apixaban\'s cost-effectiveness. Sensitivity analyses confirmed the robustness of the findings, with ICER consistently remaining below the threshold. Over 5 years (2024-2028) of Apixaban usage, the incremental cost starts at USD 70 250 296 in the first year and gradually rises to USD 71 770 662 in the fifth year. DSA and PSA were assessed to prove the robustness of the results.
CONCLUSIONS: This study shows that Apixaban is a cost-effective option for stroke prevention in non-valvular atrial fibrillation patients in Iran compared to Warfarin.

UNASSIGNED: Among patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate, a treatment sequence initiated with biosimilar disease-modifying antirheumatic drugs (DMARDs) provides better clinical efficacy compared with conventional synthetic DMARDs recommended by current treatment guidelines; but its cost-effectiveness evidence remains unclear.
UNASSIGNED: To evaluate the cost-effectiveness of the treatment sequence initiated with biosimilar DMARDs after failure with methotrexate vs leflunomide and inform formulary listing decisions.
UNASSIGNED: This economic evaluation\'s cost-effectiveness analysis was performed at a Hong Kong public institution using the Markov disease transition model to simulate the lifetime disease progression and cost for patients with RA, using monetary value in 2022. Scenario and sensitivity analyses were performed to test the internal validity of the modeling conclusion. Participants included patients diagnosed with RA from 2000 to 2021 who were retrieved retrospectively from local electronic medical records to generate model input parameters. Statistical analysis was performed from January 2023 to March 2024.
UNASSIGNED: The model assesses 3 competing treatment sequences initiated with biosimilar infliximab (CT-P13), biosimilar adalimumab (ABP-501), and leflunomide; all used in combination with methotrexate.
UNASSIGNED: Lifetime health care cost and quality-adjusted life-years (QALYs) of the simulated cohort.
UNASSIGNED: In total, 25 099 patients with RA were identified (mean [SD] age, 56 [17] years; 19 469 [72.7%] women). In the base-case analysis, the lifetime health care cost and QALYs for the treatment sequence initiated with leflunomide were US $154 632 and 14.82 QALYs, respectively; for biosimilar infliximab, they were US $152 326 and 15.35 QALYs, respectively; and for biosimilar adalimumab, they were US $145 419 and 15.55 QALYs, respectively. Both biosimilar sequences presented lower costs and greater QALYs than the leflunomide sequence. In the deterministic sensitivity analysis, the incremental cost-effectiveness ratio (US$/QALY) comparing biosimilar infliximab sequence vs leflunomide sequence and biosimilar adalimumab sequence vs leflunomide sequence ranged from -15 797 to -8615 and -9088 to 10 238, respectively, all below the predefined willingness-to-pay threshold (US $48 555/QALY gain). In the probabilistic sensitivity analysis, the probability of treatment sequence initiated with leflunomide, biosimilar infliximab, and biosmilar adalimumab being cost-effective out of 10 000 iterations was 0%, 9%, and 91%, respectively.
UNASSIGNED: In this economic evaluation study, the treatment sequences initiated with biosimilar DMARDs were cost-effective compared with the treatment sequence initiated with leflunomide in managing patients with RA who experienced failure with the initial methotrexate treatment. These results suggest the need to update clinical treatment guidelines for initiating biosimilars immediately after the failure of methotrexate for patients with RA.

BACKGROUND: Over 65s are frequent attenders to the Emergency Department (ED) and more than half are admitted for overnight stays. Early assessment and intervention by a dedicated ED-based Health and Social Care Professionals (HSCP) team reduces ED length of stay and the risk of hospital admissions among older adults while improving patient health-related quality-of-life and satisfaction with care. This study aims to evaluate whether augmenting the treatment as usual for older adults admitted to ED is cost-effective.
RESULTS: Cost-effectiveness analysis (CEA), conducted alongside the OPTI-MEND randomised controlled trial of 353 patients aged ≥65 with lower urgency complaints compared the effectiveness of early assessment and intervention by a dedicated HSCP team in the ED to treatment as usual (TAU). An economic analysis estimated the average cost per older adults randomised to the HSCP team, and compared to TAU, how contact with HSCP team changed health care use, and associated total costs, and estimated the effect of HSCP on Quality-Adjusted Life Years (QALYs). Within the OPTI-MEND trial, the average cost of a contact with the HSCP team during ED attendance is estimated to be €801 per patient. Compared to TAU, the incremental QALY of intervention is 0.053 (95% CI: 0.023 to 0.0826, p<0.0001). Accounting for cost savings because of contact with HSCP team, the average incremental saving in the total cost, compared to TAU, is -€6,128 (95% CI: -€9,217 to -€3,038, p<0.0001). Given the incremental health gains and significant cost savings, bootstrapped cost CEA suggests that dedicated HSCP care dominates over TAU for low urgency older adults attending the ED.
CONCLUSIONS: A dedicated HSCP team in the ED significantly improves overall health for lower acuity older adults and, by reducing inpatient length of stay, results in staggering cost savings. This economic evaluation conducted on the OPTI-MEND trial provides convincing evidence that HSCP should be adopted as part of treatment as usual in Irish EDs.
BACKGROUND: ClinicalTrials.gov, NCT03739515; registered on 12th November 2018. https://classic.clinicaltrials.gov/ct2/show/NCT03739515.

BACKGROUND: Chronic migraine (CM) is the most severe and burdensome subtype of migraine. Fremanezumab is a monoclonal antibody that targets the calcitonin gene-related peptide pathway as a migraine preventive therapy. This study aimed to conduct a cost-effectiveness analysis of fremanezumab from a societal perspective in the Netherlands, using a Markov cohort simulation model.
METHODS: The base-case cost-effectiveness analysis adhered to the Netherlands Authority guidelines. Fremanezumab was compared with best supportive care (BSC; acute migraine treatment only) in patients with CM and an inadequate response to topiramate or valproate and onabotulinumtoxinA (Dutch patient group [DPG]). A supportive analysis was conducted in the broader group of CM patients with prior inadequate response to 2-4 different classes of migraine preventive treatments. One-way sensitivity, probabilistic sensitivity, and scenario analyses were conducted.
RESULTS: Over a lifetime horizon, fremanezumab is cost saving compared with BSC in the DPG (saving of €2514 per patient) and led to an increase of 1.45 quality-adjusted life-years (QALYs). In the broader supportive analysis, fremanezumab was cost effective compared with BSC, with an incremental cost-effectiveness ratio of €2547/QALY gained. Fremanezumab remained cost effective in all sensitivity and scenario analyses.
CONCLUSIONS: In comparison to BSC, fremanezumab is cost saving in the DPG and cost effective in the broader population.

Patients with PD-L1-positive esophageal squamous-cell carcinoma (ESCC) were significantly more likely to survive when treated with serplulimab plus cisplatin plus 5-fluorouracil (serplulimab-CF). At this point, it is unknown whether this expensive therapy is cost-effective. From the Chinese healthcare system\'s perspective, we aimed to evaluate serplulimab-CF versus CF alone for cost-effectiveness. A partitioned survival model was constructed based on the ASTRUM-007 trial. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. A further analysis of subgroups and scenarios was conducted. The willingness to pay (WTP) threshold of $38,258/QALY or $84,866/QALY is defined as three times the per capita gross domestic product value of the general region or affluent region. Compared with CF alone, in the overall (scenario 1), patients with PD-L1 expression level of 1 ≤ CPS < 10 (scenario 2), and patients with PD-L1 CPS ≥ 10 (scenario 3) populations, the ICERs were $69,025/QALY, $82,533/QALY, and $75,436/QALY for serplulimab-CF. Nevertheless, the probability of serplulimab-CF becoming cost-effective based on scenarios 1, 2, and 3 is only 2.71%, 0.94%, and 2.84%, respectively, at a WTP threshold of $38,258/QALY. When serplulimab costs < $4.84/mg, serplulimab-CF may be cost-effective at the WTP threshold of $38,258/QALY; otherwise, CF was preferred. Similar results were obtained from sensitivity analyses, suggesting the robustness of these findings. There was no cost-effectiveness in general regions of China for serplulimab-CF in PD-L1-positive ESCC compared to CF, although it is probably considered cost-effective in affluent regions. Serplulimab-CF may achieve favorable cost-effectiveness by lowering the price of serplulimab.